DOI: 10.1101/gad.1397906. Specific functional interactions of nucleotides at key <sup>-</sup>3 and <sup>+</sup>4 positions flanking the initiation codon with components of the mammalian 48S translation initiation complex

Specific functional interactions of nucleotides at key -3 and +4 positions flanking the initiation codon with components of the mammalian 48S translation initiation complex

10.1101/gad.1397906

Crossref journal-article

Cold Spring Harbor Laboratory

Genes & Development (246)

Abstract

Eukaryotic initiation factor (eIF) 1 maintains the fidelity of initiation codon selection and enables mammalian 43S preinitiation complexes to discriminate against AUG codons with a context that deviates from the optimum sequence GCC(A/G)CCAUGG, in which the purines at -3 and +4 positions are most important. We hypothesize that eIF1 acts by antagonizing conformational changes that occur in ribosomal complexes upon codon-anticodon base-pairing during 48S initiation complex formation, and that the role of -3 and +4 context nucleotides is to stabilize these changes by interacting with components of this complex. Here we report that U and G at +4 both UV-cross-linked to ribosomal protein (rp) S15 in 48S complexes. However, whereas U cross-linked strongly to C1696 and less well to AA1818-1819 in helix 44 of 18S rRNA, G cross-linked exclusively to AA1818-1819. U at -3 cross-linked to rpS5 and eIF2α, whereas G cross-linked only to eIF2α. Results of UV cross-linking experiments and of assays of 48S complex formation done using α-subunit-deficient eIF2 indicate that eIF2α's interaction with the -3 purine is responsible for recognition of the -3 context position by 43S complexes and suggest that the +4 purine/AA1818-1819 interaction might be responsible for recognizing the +4 position.

Bibliography

Pisarev, A. V., Kolupaeva, V. G., Pisareva, V. P., Merrick, W. C., Hellen, C. U. T., & Pestova, T. V. (2006). Specific functional interactions of nucleotides at key -3 and +4 positions flanking the initiation codon with components of the mammalian 48S translation initiation complex. Genes & Development, 20(5), 624â636.

Authors 6

Andrey V. Pisarev (first)
Victoria G. Kolupaeva (additional)
Vera P. Pisareva (additional)
William C. Merrick (additional)
Christopher U.T. Hellen (additional)
Tatyana V. Pestova (additional)

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Dates

Type	When
Created	19 years, 5 months ago (March 1, 2006, 6:33 p.m.)
Deposited	3 years, 9 months ago (Nov. 16, 2021, 12:07 p.m.)
Indexed	6 days, 15 hours ago (Aug. 20, 2025, 8:25 a.m.)
Issued	19 years, 5 months ago (March 1, 2006)
Published	19 years, 5 months ago (March 1, 2006)
Published Online	19 years, 5 months ago (March 1, 2006)
Published Print	19 years, 5 months ago (March 1, 2006)

Funders 0

None

BibTeX

@article{Pisarev_2006, title={Specific functional interactions of nucleotides at key -3 and +4 positions flanking the initiation codon with components of the mammalian 48S translation initiation complex}, volume={20}, ISSN={1549-5477}, url={http://dx.doi.org/10.1101/gad.1397906}, DOI={10.1101/gad.1397906}, number={5}, journal={Genes & Development}, publisher={Cold Spring Harbor Laboratory}, author={Pisarev, Andrey V. and Kolupaeva, Victoria G. and Pisareva, Vera P. and Merrick, William C. and Hellen, Christopher U.T. and Pestova, Tatyana V.}, year={2006}, month=mar, pages={624–636} }

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